Objectives Develop PET imaging technology to study AIDS pathogenesis ABSTRACT:Pathogenesis of simian immunodeficiency virus (SIV) infection in rhesus macaques begins with acute viremia, then a distributed infection in the solid lymphoid tissues, followed by a process of cellular destruction leading to terminal disease and death. Blood and tissue specimens show the progress of infection at the cellular level but do not reveal the pattern of infection and host responses occurring throughout the body. The purpose of this investigation was to determine whether positron emission tomography imaging with intravenous 18F-2-fluoro-2-deoxyglucose (PET-FDG) could identify activated lymphoid tissues in a living animal and whether this pattern would reflect the extent of SIV infection. PET images from SIV-infected animals were distinguishable from uninfected controls and revealed a pattern consistent with widespread lymphoid tissue activation. Significant FDG accumulation in colon along with mesenteric and ileocaecal lymph nodes was found in SIV infection especially during terminal disease stages. Areas of elevated FDG uptake in the PET images were correlated with productive SIV infection using in situ hybridization as a test for virus replication. PET-FDG images of SIV-infected animals correlated sites of virus replication with high FDG accumulation. These data show that the method can be used to evaluate the distribution and activity of infected tissues in a living animal without biopsy. Fewer tissues had high FDG uptake in terminal animals than mid-stage animals and both were clearly distinguishable from uninfected animal scans. Simialr results were obtained recently in seven imagin experiments with HIV-positive patients. Volume rendering reconstructions of these data with video viewing of rotated images is improving utility of PET/FDG images obtained from clinical studies. Keywords AIDS, HIV; SIV; lymph node